When macromolecules, such as horseradish peroxidase (HRP), are injected into the blood, they are prevented from entering CSF and extracellular fluid of the brain by the blood-brain and blood-CSF barriers: the tight junctions of cerebral endothelium and choroid plexus epithelium account, respectively, for these exclusions. Both barriers are circumvented by transplanting pieces of superior cervical ganglia (SCG) to the intact surface of the brain because (i) the capillaries of ganglia are fenestrated and permeable to protein, (ii) the extra-cellular clefts of the SCG become confluent with those of brain and (iii) there are no belts of tight junctions between normal or reactive astrocytes of the subpial glia to prevent the extracellular penetration of macromolecules from blood into brain. The extracellular compartment of a peripheral ganglion transplant becomes perfectly confluent with that of the brain and is thus able to transfer blood-borne molecules into brain.